title: MECP2 gene study in a large cohort: testing of 240 female patients and 861 healthy controls (519 females and 342 males).
abstract: The MECP2 gene located on Xq28 is one of the most important genes contributing to the spectrum of neurodevelopmental disorders. Therefore, we present our experience in the molecular study of this gene. MECP2 was thoroughly tested for the presence of mutations (sequencing of four exons and rearrangements) in 120 female patients: 28 with classic Rett syndrome, five with atypical Rett syndrome, and 87 with heterogeneous phenotypes with some Rett-like features. Another 120 female patients with intellectual disability of unknown origin were also studied, but in these cases we only tested exons 3 and 4. Finally, 861 healthy controls (519 females and 342 males) were also studied for exon 3 and 4. Eighteen different pathological mutations were found, five of them previously undescribed, and four large deletions detected by multiplex ligation-dependent probe amplification. All were de novo mutations not present in the parents. In conclusion, i) MECP2 is one of the most important genes in the diagnosis of genetic intellectual disability in females; ii) MECP2 must be studied not only in patients with classical/atypical Rett syndrome but also in patients with other phenotypes related to Rett syndrome; and iii) for the new variants, it is important to perform complementary studies, including the analysis of large populations of healthy individuals and the use of in silico programs.
authors.affiliation: Molecular Genetics Laboratory, Genetics Service, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo-Bizkaia, Spain.
authors.forename: Hiart
authors.initials: H
authors.lastname: Maortua
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Ainhoa
authors.initials: A
authors.lastname: García-Ribes
authors.forename: María-Jesus
authors.initials: MJ
authors.lastname: Martínez
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillen
authors.forename: María-Rosario
authors.initials: MR
authors.lastname: Domingo
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Gabau
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: Botella
authors.forename: Blanca
authors.initials: B
authors.lastname: Gener
authors.forename: Izaskun
authors.initials: I
authors.lastname: Rubio
authors.forename: María-Asunción
authors.initials: MA
authors.lastname: López-Aríztegui
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
mesh_terms: D016022:Case-Control Studies; D019295:Computational Biology; D005091:Exons; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics
chemical_list: D051783:Methyl-CpG-Binding Protein 2